title: The role of innate immunity in promoting SaeR/S-mediated virulence in Staphylococcus aureus.
abstract: The ability of Staphylococcus aureus to infect tissues is dependent on precise control of virulence through gene-regulatory systems. While the SaeR/S two-component system has been shown to be a major regulator of S. aureus virulence, the influence of the host environment on SaeR/S-regulated genes (saeR/S targets) remains incompletely defined. Using QuantiGene 2.0 transcriptional assays, we examined expression of genes with the SaeR binding site in USA300 exposed to human and mouse neutrophils and host-derived peptides and during subcutaneous skin infection. We found that only some of the saeR/S targets, as opposed to the entire SaeR/S virulon, were activated within 5 and 10 min of interacting with human neutrophils as well as α-defensin. Furthermore, mouse neutrophils promoted transcription of saeR/S targets despite lacking α-defensin, and the murine skin environment elicited a distinctive expression profile of saeR/S targets. These findings indicate that saeR/S-mediated transcription is unique to and dependent on specific host stimuli. By using isogenic USA300ΔsaeR/S and USA300Δagr knockout strains, we also determined that SaeR/S is the major regulator of virulence factors, while Agr, a quorum-sensing two-component system, has moderate influence on transcription of the saeR/S targets under the tested physiological conditions.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Mont., USA.
authors.forename: Oliwia W
authors.initials: OW
authors.lastname: Zurek
authors.forename: Tyler K
authors.initials: TK
authors.lastname: Nygaard
authors.forename: Robert L
authors.initials: RL
authors.lastname: Watkins
authors.forename: Kyler B
authors.initials: KB
authors.lastname: Pallister
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D046228:Microarray Analysis; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D012867:Skin / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D015534:Trans-Activators; D014157:Transcription Factors; D059467:Transcriptome; D014774:Virulence / Q000235:genetics; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; C433805:SaeR protein, Staphylococcus aureus; D015534:Trans-Activators; D014157:Transcription Factors; D023084:alpha-Defensins